利用生长因子、促进素和人肾上腺皮质细胞株细胞培养基来诱导人类诱导多能干细胞(hiPSC)分化所得细胞的基因表达谱研究。
Gene expression profile of hiPSC-derived cells differentiated with growth factors, forskolin and conditioned medium from human adrenocortical cell line.
发表日期:2023 Aug 04
作者:
Ewelina Stelcer, Karol Jopek, Małgorzata Blatkiewicz, Anna Olechnowicz, Kacper Kamiński, Marta Szyszka, Wiktoria Maria Suchorska, Marcin Ruciński
来源:
Stem Cell Research & Therapy
摘要:
肾上腺皮质癌(ACC)在美国每百万人中大约影响2人,女性患病率高于男性。肾上腺皮质癌通常会伴随严重症状,如腹痛、高血压、痤疮、毛发过度生长和声音变低。关于ACC的研究构成了大量已发表的数据。对ACC来源的生物材料的易于获取性需求增加。此外,人类细胞株的数量有限。出于这个原因,我们尝试将人类诱导多能干细胞(hiPSCs)分化为肾上腺皮质类细胞以建立一种新的功能性细胞株。我们在生长因子(GFs)、促进素和人类肾上腺癌(HAC15)细胞株收集的条件培养基的存在下进行了长期分化过程(35和70天)。然后,我们分析了分化细胞的基因表达谱。所获得的细胞具有三个原始胚层的特征。有趣的是,分化细胞在内分泌过程中的基因表达水平极高,特别是糖蛋白激素α多肽(CGA)、胰岛素受体底物4(IRS4)和胰腺前体细胞分化与增殖因子样蛋白(PPDPFL)。研究结果表明,我们获得了来源于内胚层且具有胰腺样细胞某些特征的前体细胞。内胚层分化是一个非常具有挑战性和复杂性的过程,因此本研究中呈现的结果值得更加仔细地考虑。
Adrenocortical carcinoma (ACC) affects approx. 2 in 1,000,000 individuals in the USA, and is more common in females than males. Adrenocortical carcinoma often presents with severe symptoms, such as abdominal pain, high blood pressure, acne, hair overgrowth, and voice deepening.Research on ACC constitutes a large body of published data. There is an increased need for easy access to ACC-derived biological material. Moreover, there are limited numbers of human cell lines available. For this reason, we attempted to differentiate human induced pluripotent stem cells (hiPSCs) into adrenocortical-like cells to establish a new functional cell line.We conducted a long-term differentiation process (35 and 70 days) in the presence of growth factors (GFs), forskolin and conditioned medium collected from the human adrenal carcinoma (HAC15) cell line. Then, we analyzed the gene expression profile of the differentiated cells.The obtained cells possess features characteristic of all 3 primary germ layers. Interestingly, the differentiated cells demonstrated an extremely high level of gene expression for those involved in endocrine processes, namely glycoprotein hormones, alpha polypeptide (CGA), insulin receptor substrate 4 (IRS4), and pancreatic progenitor cell differentiation and proliferation factor-like protein (PPDPFL).The results of the study indicate that we obtained progenitors derived from endoderm with some characteristics of pancreatic-like cells. The endodermal derivative differentiation is a very challenging and complicated process; thus, the results presented in this study deserve closer consideration.